A selective retrieval procedure will be developed for studying the composition and organization of biological membranes. The method is based on the enzyme-catalyzed incorporation of biotin derivatives onto the plasma membrane of intact cells. The tagged components will be isolated by virtue of their specific interaction with avidin. The essentially covalent character of the avidin-biotin complex will be disrupted by the use of biotin analogs with modification to the imidazolidone ring system. The ability to specifically retrieve labeled membrane components will facilitate research in certain areas of membrane biology. For example, it will be possible to investigate the composition of normal and altered mammalian cells without the isolation and purification of their plasma membranes. Electron dense and fluorescent avidin derivatives can be used to probe the spatial distribution of the labeled components on the cell surface prior to the solubilization of the membrane. Nearest neighbor analysis of membrane components will be simplified considerably by the ability to recover only the complexes formed amongst the tagged components and their neighbors. The applicability of the method will be tested initially on two model systems: (a) the erythrocyte membrane and (b) the mitochondria. In future studies, the methods will be used to investigate the alterations that occurred to the plasma membrane of spermatozoa during epididymal maturation and also during capacitation.